U.S. patent application number 17/343837 was filed with the patent office on 2022-01-06 for microscope for microscopic examination of a sample.
The applicant listed for this patent is Leica Microsystems CMS GmbH. Invention is credited to Stefan CHRIST.
Application Number | 20220001380 17/343837 |
Document ID | / |
Family ID | |
Filed Date | 2022-01-06 |
United States Patent
Application |
20220001380 |
Kind Code |
A1 |
CHRIST; Stefan |
January 6, 2022 |
MICROSCOPE FOR MICROSCOPIC EXAMINATION OF A SAMPLE
Abstract
A microscope for microscopic examination of a sample includes: a
microscope housing enclosing an illumination optics, a microscope
stage, and an imaging optics; an integrated sample chamber located
within the microscope housing; and an integrated reagent chamber
located within the microscope housing, the integrated reagent
chamber supplying a reagent to the sample.
Inventors: |
CHRIST; Stefan;
(Schoeffengrund, DE) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Leica Microsystems CMS GmbH |
Wetzlar |
|
DE |
|
|
Appl. No.: |
17/343837 |
Filed: |
June 10, 2021 |
International
Class: |
B01L 3/00 20060101
B01L003/00 |
Foreign Application Data
Date |
Code |
Application Number |
Jul 3, 2020 |
EP |
20184081.6 |
Claims
1. A microscope for microscopic examination of a sample,
comprising: a microscope housing enclosing an illumination optics,
a microscope stage, and an imaging optics; an integrated sample
chamber located within the microscope housing; and an integrated
reagent chamber located within the microscope housing, the
integrated reagent chamber being configured to supply a reagent to
the sample.
2. The microscope of claim 1, wherein the reagent chamber is
located outside the sample chamber and comprises a connecting tube
connecting the reagent chamber with the sample chamber.
3. The microscope of claim 2, wherein the connecting tube
comprises, at a first tube end thereof, a plug at configured to at
least partly close the first tube end.
4. The microscope of claim 1, wherein the reagent chamber is
located within the sample chamber.
5. The microscope of claim 4, wherein the reagent chamber comprises
an opening at least partly closed by a plug.
6. The microscope of claim 1, wherein the reagent chamber is at
least one of thermally insulated and light protected.
7. The microscope of claim 1, wherein the reagent chamber is
temperature controlled.
8. The microscope of claim 7, wherein the reagent chamber comprises
at least one of a cooling unit, a heating unit, and a heat
exchanging unit.
9. The microscope of claim 7, wherein the reagent chamber comprises
a Peltier element.
10. The microscope of claim 7, wherein the reagent chamber
comprises a coolpack.
11. The microscope of claim 1, wherein the reagent chamber is
connected to a temperature control unit configured to control a
temperature inside the reagent chamber.
12. The microscope of claim 11, wherein the temperature control
unit comprises at least one of a fan, a cooling unit, a heating
unit, and a heat exchanging unit.
13. The microscope of claim 3, wherein the reagent chamber is
configured such that at least one reagent container is installable
in the reagent chamber.
14. The microscope of claim 13, wherein the reagent chamber is
configured such that at least one of a reagent supply line and a
reagent removal line are connectable to one of the least one
reagent container.
15. The microscope of claim 14, wherein the plug is configured to
duct the at least one of the reagent supply line and the reagent
removal line through the plug.
16. The microscope of claim 14, wherein the reagent chamber
comprises a pump system configured to convey reagent through the
reagent supply line and/or the reagent removal line.
17. The microscope of claim 1, wherein the reagent chamber
comprises a door configured to provide access into the reagent
chamber.
Description
CROSS-REFERENCE TO PRIOR APPLICATION
[0001] Priority is claimed to European Patent Application No. EP
20184081.6, filed on Jul. 3, 2020, the entire disclosure of which
is hereby incorporated by reference herein.
FIELD
[0002] The present inventive concept is directed to a microscope
for microscopic examination of a sample, particularly for
examination of a sample to be located in a sample chamber where a
reagent is to be supplied to the sample before or during
examination of the sample.
BACKGROUND
[0003] Especially in the field of microscopic examination of living
samples like cells, it is common practice to supply a reagent to
the sample before microscopic examination of the sample. A reagent
in the meaning of the present application encompasses any fluids,
in particular liquids with or without chemically or biologically
active substances, e.g. water, water-soluble or fat-soluble or
other substances like hormones or medicine in a suitable carrier
substance for triggering biological or chemical reactions with the
sample or just for preserving the sample. Usually, the sample
itself is located in multi-well-plates, Petri dishes or
microfluidic systems on a microscope table. Pumps are used for
supplying the reagent to the sample. Syringe pumps are often used
for injection processes and peristaltic pumps are used for
continuously conveying a reagent, for example for supplying a
reagent to a sample and simultaneously removing reagent from the
sample. On the other hand, manual pipetting can be carried out.
[0004] Various kinds of containers, like Falcon tubes or Eppendorf
tubes or Schott flasks, are used for storing the reagent. The
containers are typically located outside the microscope housing,
sometimes in a temperature controlled box. One ore more pump
systems are used for transporting reagent from a container to the
sample, the pump system typically being either located outside the
microscope housing or inside the microscope housing. Temperature
controlled boxes for storage of reagent containers typically
include heating elements or ice baths.
[0005] In many cases, only small amounts of a reagent need to be
injected into a biological sample and the reagent has to be stored
in a light protected container at a temperature below ambient
temperature, for example at 4 to 8.degree. C. This especially
applies to the injection of stimulants, like hormones or medicine
drugs, in 3D-cell-culture experiments. Supplying the reagent
through long supply lines makes it difficult to keep the reagent
light protected and at a certain temperature on its way to the
sample. Further, a lot of fluid is needed to compensate for the
dead volume inside the tubing, which in turn generates higher costs
for the chemicals in use.
[0006] On the other hand, larger amounts of reagent need to be
exchanged for example in organ-on-a-chip experiments. Injection of
larger amounts of reagent or linking of a peristaltic pump system
is often cumbersome and--due to differences in temperature of the
reagent to be injected and the sample to be examined--can result in
temperature dependent measurement artefacts and even in a dieback
of the sample during the experiment. Thus, ideally, the temperature
of the reagent to be injected should be the same as the temperature
of the sample.
SUMMARY
[0007] In an embodiment, the present invention provides a
microscope for microscopic examination of a sample, comprising: a
microscope housing enclosing an illumination optics, a microscope
stage, and an imaging optics; an integrated sample chamber located
within the microscope housing; and an integrated reagent chamber
located within the microscope housing, the integrated reagent
chamber being configured to supply a reagent to the sample.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] The present invention will be described in even greater
detail below based on the exemplary figures. The invention is not
limited to the exemplary embodiments. Other features and advantages
of various embodiments of the present invention will become
apparent by reading the following detailed description with
reference to the attached drawings which illustrate the
following:
[0009] FIG. 1 schematically shows a first embodiment of a
microscope including a reagent chamber located outside the sample
chamber of the microscope;
[0010] FIG. 2 schematically shows a further embodiment of a
microscope including a reagent chamber located inside the sample
chamber of the microscope;
[0011] FIG. 3 schematically shows a further embodiment of a
microscope including a reagent chamber located outside the sample
chamber of the microscope;
[0012] FIG. 4 schematically shows a further embodiment of a
microscope including a reagent chamber located outside the sample
chamber of the microscope;
[0013] FIG. 5 schematically shows a further embodiment of a
microscope including a reagent chamber and a temperature control
unit, both located outside the sample chamber of the
microscope;
[0014] FIG. 6 schematically shows a further embodiment of a
microscope including a reagent chamber and a temperature control
unit, both located outside the sample chamber of the microscope;
and
[0015] FIG. 7 schematically shows a further embodiment of a
microscope including a reagent chamber located outside the sample
chamber of the microscope.
DETAILED DESCRIPTION
[0016] In view of the drawbacks described above, there is a need
for an improved solution for supplying reagents to a sample which
is examined in a microscope.
[0017] Embodiments of present inventive concept provide a
microscope for microscopic examination of a sample as described
herein. The microscope comprises a microscope housing enclosing an
illumination optics, a microscope stage and an imaging optics, and
further an integrated sample chamber located within the microscope
housing. Further, an integrated reagent chamber is located within
the same microscope housing and configured to supply a reagent to
the sample.
[0018] The present inventive concept can thus provide a microscope
including an integrated reagent chamber which is located together
with the integrated sample chamber within the same microscope
housing. This solution allows minimum distances between a reagent
container and the sample. At the same time, the reagent can be
conveyed and stored in a light protected manner and with little or
no temperature fluctuation. Another advantage is that reagent can
be supplied to the sample before and/or during examination without
the need of accessing the sample by a user.
[0019] It should be noted that the reagent chamber according to the
present inventive concept is configured to supply a reagent to the
sample. This means that the required reagent containers which may
also be buffer containers and, preferably, the associated pump
systems together with the corresponding reagent supply lines can be
installed in or are part of the reagent chamber.
[0020] In a preferred embodiment, the reagent chamber itself is
light protected and/or thermally insulated. In this embodiment,
ambient atmosphere exerts minimum influence on the reagent inside
the reagent chamber.
[0021] There are two alternatives for locating the integrated
reagent chamber within the microscope housing, namely the reagent
chamber can be located outside or inside the sample chamber.
[0022] In case the reagent chamber is located outside the sample
chamber, the reagent chamber comprises a connecting tube connecting
the reagent chamber with the sample chamber. As the reagent chamber
and the sample chamber in this embodiment represent separated
entities, it is highly preferable that the reagent chamber
including the connecting tube is thermally insulated. In a
preferred embodiment, the reagent chamber contains at least one
reagent container and a pump system for conveying the reagent from
the reagent container through at least one reagent supply line to
the sample located within the sample chamber. The at least one
supply line and/or any reagent removal lines extend through the
connecting tube.
[0023] In a preferred embodiment, the connecting tube comprises a
plug at at least one of its ends for (at least) partly closing the
respective tube end. The plug, for example, is inserted into the
end of the connecting tube facing the sample chamber. The plug is
formed such that any supply/removal lines can still extend through
the plug through corresponding through holes. Such a plug serves
the purpose of defining predetermined positions of the
supply/removal lines and of providing a high thermal insulation and
of preventing sample chamber atmosphere entering the reagent
chamber.
[0024] According to the second alternative, the reagent chamber is
located within the sample chamber. This embodiment is especially
preferred in cases where the sample chamber provides enough space
for accommodating the reagent chamber. Mostly, especially in the
case of biological samples, the sample chamber is incubated, i.e.
temperature and incubation atmosphere composition within the sample
chamber are controlled. In such cases it might not be necessary to
use a thermally insulated reagent chamber as the temperature of the
non-insulated reagent chamber will approach the temperature of the
incubated sample chamber. Nevertheless, it is preferred if the
reagent chamber comprises an opening at least partly closed by a
plug. As already explained above in connection with the first
alternative, the plug can serve the purpose of determining a
defined position of any supply/removal lines. Further it increases
the insulation efficiency of an insulated reagent chamber. Finally,
it avoids that the incubation atmosphere enters the interior of the
reagent chamber.
[0025] It should be noted that there are cases where a stage top
chamber is used which is placed within the sample chamber onto the
microscope stage and which is configured to receive the sample. In
such cases, only the very small volume of the stage top chamber is
incubated. In these cases, the reagent supply line has to be
connected to the stage top chamber such that reagent is supplied to
the sample within the stage top chamber. Equally, a reagent removal
line has to be connected to the stage top chamber such that reagent
can be removed from the sample, e.g. back to the reagent
chamber.
[0026] In another preferred embodiment of the microscope, the
integrated sample chamber is formed by a separated housing section
within the microscope housing. This housing section forming the
sample chamber comprises a lid providing direct access to the
microscope stage for placing the sample in the sample chamber.
Further, the integrated reagent chamber can be formed by another
separated housing section within said microscope housing, this
further housing section comprising another door providing direct
access to the at least one reagent container and/or the pump
system. By opening the door, a user can refill a reagent container,
exchange a reagent container, exchange or adjust the pump system,
and connect a reagent supply/removal line.
[0027] In another preferred embodiment, the housing section forming
the sample chamber is configured such that, when the lid is closed,
the sample chamber is sealed. This is especially advantageous if
the reagent chamber is located within the sample chamber and if the
sample chamber is incubated. By using a non-insulated reagent
chamber, the temperature in the sample chamber and in the reagent
chamber will average out such that no temperature difference exists
between the reagent and the sample.
[0028] In another preferred embodiment, the housing section forming
the sample chamber encloses the illumination optics of the
microscope and, at least partly, the microscope stage. Such a
configuration corresponds to an inverse transmitted-light
microscope. Still another housing section may enclose the imaging
optics of the microscope.
[0029] In a preferred embodiment, the reagent chamber is configured
to be temperature controlled. It is especially useful to
temperature control the reagent chamber if the reagent chamber is
thermally insulated. This allows to maintain a predefined
temperature within the reagent chamber such that any reagent in a
container, a supply line or a pump can be kept at a desired
temperature. Generally, it might be expedient to configure any of
said housing sections, namely the sample chamber, the reagent
chamber and the section enclosing the imaging optics, to be
air-conditioned or incubated and/or temperature-controlled.
[0030] In regard to a possible incubation of the sample chamber, it
is preferred if the housing section forming the sample chamber
comprises an interface for connection of an external incubation
environment conditioning unit to the sample chamber. This allows
the environmental conditions in the sample chamber to be controlled
when the external incubation environment conditioning unit is
connected to the interface. Typically, the incubation environment
conditioning unit comprises a connection for supplying H.sub.2O, a
connection for discharging H.sub.2O and/or incubation atmosphere, a
connection for supplying Na and/or O.sub.2, and a connection for
supplying CO.sub.2 into the sample chamber. A desired incubation
atmosphere is achieved by controlling at least one of a flow rate
and a temperature and content of H.sub.2O and/or CO.sub.2 and/or
N.sub.2 and/or O.sub.2 of the incubation atmosphere supplied into
the sample chamber.
[0031] Temperature control of the reagent chamber can be achieved
by at least one of a cooling unit, a heating unit and a heat
exchanging unit located within the reagent chamber. Preferably, a
Peltier element can be used as a cooling and heating unit. On the
other hand, the cooling unit can simply be a coolpack located
within the reagent chamber. Also, a heat exchanger can be used for
heating or cooling the atmosphere within the reagent chamber
against a heat transfer medium in the heat exchanger.
[0032] In another embodiment, the reagent chamber is connected to a
temperature control unit configured to control a temperature inside
the reagent chamber. The temperature control unit can be located
outside, e.g. next to the reagent chamber with an atmosphere
connecting tube for exchanging atmosphere between the temperature
control unit and the reagent chamber. To this end, it is preferred
if the temperature control unit comprises at least one fan for
circulating heated or cooled atmosphere between the temperature
control unit and the reagent chamber. Again, a cooling unit, a
heating unit and/or a heat exchanging unit can be provided in the
temperature control unit for achieving a desired temperature of the
atmosphere exchanged between the temperature control unit and the
reagent chamber.
[0033] As already discussed above, in a preferred embodiment, the
reagent chamber is configured such that at least one reagent
container can be installed in the reagent chamber. In operation,
the microscope includes a reagent chamber comprising at least one
reagent container. Further, it is preferred that the reagent
chamber is configured such that at least one of a reagent supply
line and a reagent removal line can be connected to one of the at
least one reagent container. Again, in operation of the microscope,
the reagent chamber comprises at least one of a reagent supply line
and a reagent removal line connected to a reagent container. In
case of more than one reagent container, a plurality of
supply/removal lines can be present.
[0034] In a preferred embodiment, the plug in the connecting tube
in the first alternative, or the plug at the opening of the reagent
chamber in the second alternative, is configured to duct a reagent
supply line and/or a reagent removal line through the plug.
[0035] Further, the reagent chamber preferably comprises a pump
system for conveying reagent through the reagent supply and/or
removal line(s). The pump system may comprise a syringe pump and/or
a peristaltic pump.
[0036] Finally, it is preferred that the reagent chamber comprises
a door providing access into the reagent chamber.
[0037] It should be noted that features of the above examples and
embodiments as well as of the examples and embodiments explained
further below can--wholly or in part--be combined to other examples
and embodiments not explicitly mentioned herein, nevertheless being
part of the present disclosure.
[0038] FIG. 1 schematically shows an embodiment of a microscope
according to the present inventive concept. A microscope 100 for
microscopic examination of a sample 120 comprises a microscope
housing 102 enclosing an illumination optics 118, a microscope
stage 116 and an imaging optics 124. An integrated sample chamber
106 is located within the microscope housing 102. The configuration
shown in FIG. 1 corresponds to an inverse transmitted-light
microscope wherein the sample 120 is illuminated by the
illumination optics 118 and light transmitted through the sample
120 is detected by the imaging optics 124. In a preferred
embodiment, the sample chamber 106 is formed by a separated housing
section 104 within the microscope housing 102. Typically, the
sample chamber 106 is incubated in order to maintain a desired
incubation atmosphere and temperature during examination of the
sample 120.
[0039] In the embodiment shown in FIG. 1, the reagent chamber 150
is located outside the sample chamber 106 and comprises a
connecting tube 170 connecting the reagent chamber 150 with the
sample chamber 106. The reagent chamber 150 is located within the
microscope housing 102 and is configured to supply a reagent to the
sample 120. The reagent chamber can be formed by another housing
section of the microscope housing 102. The reagent chamber 150
comprises a door 152 providing direct access into the reagent
chamber 150 by a user of the microscope 100. The connecting tube
170 comprises a plug 172 at the end of the connecting tube 170
facing the sample chamber 106. The plug 172 partly closes the
respective tube in order to prevent incubation atmosphere from
entering the reagent chamber 150. It is preferred, especially in
the configuration shown in FIG. 1, if the reagent chamber 150
including the connecting tube 170 is thermally insulated and light
protected. This allows to preserve the reagents located in the
reagent chamber and to maintain a desired temperature within the
reagent chamber 150.
[0040] FIG. 2 schematically shows another embodiment of a
microscope according to the present inventive concept. As can be
seen in FIG. 2, the reagent chamber 150 is integrated into the
sample chamber 106 within the microscope housing 102. The sample
chamber 106, in this embodiment, is formed by a separated housing
section 104 of the microscope housing 102. In this housing section
104, there is located the illumination optics 118 and a part of the
microscope stage 116 for carrying the sample 120. In another
housing section below housing section 104, the imaging optics 124
is located. As in the embodiment in FIG. 1, the microscope of FIG.
2 is an inverse transmitted-light microscope. It should be noted,
however, that the present inventive concept is not limited to this
type of microscope.
[0041] In the embodiment shown in FIG. 2, the sample 120 is located
within a stage top chamber 210 which is placed onto the microscope
stage 116. Depending on the kind of experiment, the sample 120 may
be placed directly onto the microscope stage 116 without such a
stage top chamber 210. When using a stage top chamber 210, it is
expedient not to incubate the whole sample chamber 106 but only the
small volume of the stage top chamber 210.
[0042] The reagent chamber 150, in the embodiment shown in FIG. 2,
is formed as a thermally insulated chamber comprising a closable
door for direct access into the reagent chamber 150. Various
possibilities of interior fittings of the reagent chamber 150 of
the embodiments of FIGS. 1 and 2 will be discussed further below in
connection with the following Figures. The reagent chamber 150
comprises an opening 252 partly closed by a plug 272 for insulation
reasons. A supply line 254 for supplying a reagent into the stage
top chamber 210 extends from a reagent container through the plug
272 into the stage top chamber 210.
[0043] In the embodiment shown in FIG. 2, the reagent chamber 150
comprises another opening 112 working as a cable duct which can be
used for e.g. power cords, trigger cables, and/or a connection to
an external temperature control unit (as will be explained further
below in connection with the following Figures). This opening 112
may also be partly closed by another plug comprising through holes
for the corresponding cables etc.
[0044] It should be noted that FIGS. 1 and 2 show the basic
principles of the two alternatives of possible arrangements of the
integrated reagent chamber within the microscope housing, while the
following Figures will more focus on possible interior fittings as
well as on the temperature control of the reagent chamber 150
itself. It should be noted that the following embodiments can be
combined with each alternative embodiment shown in FIG. 1 or in
FIG. 2.
[0045] FIG. 3 shows another embodiment of a microscope according to
the present inventive concept in the alternative corresponding to
FIG. 1 as discussed above. Thus, only the differences in regard to
FIG. 1 are discussed for reasons of conciseness.
[0046] The reagent chamber 150 in FIG. 3 comprises a reagent
container 380 in the form of a Falcon tube, a pump system 374 in
the form of a perfusor or syringe pump, and a reagent supply line
254. A coolpack 360 as a cooling unit is arranged at the backside
of the reagent chamber 150. This allows to maintain a temperature
below ambient temperature within the insulated reagent chamber 150.
The cooled reagent can be conveyed by the perfusor 374 from the
Falcon tube 380 to the sample 120 through the supply line 254.
[0047] FIG. 4 shows a slightly different embodiment of the
embodiment in FIG. 3. Instead of a coolpack 350, a Peltier element
458 is installed at or into the outer wall of the reagent chamber
150 for cooling or heating the inside of the reagent chamber 150.
Such a Peltier element 458 can easily be used for controlling the
temperature within the reagent chamber 150 to a desired temperature
by use of corresponding temperature sensors within the reagent
chamber.
[0048] FIG. 5 shows another embodiment of a reagent chamber 150
which is connected to a temperature control unit 562. Apart from
that, the embodiment of FIG. 5 corresponds to the embodiments of
FIGS. 3 and 4. Instead of having a coolpack 360 or a Peltier
element 458, the temperature in the reagent chamber 150 is
controlled by connecting a temperature control unit 562 to the
reagent chamber 150. The temperature control unit 562 comprises a
fan 564, a Peltier element 458 and a heating unit 566. Instead of
the heating unit 566 a heat exchanging unit can be used. It should
be noted that, depending on the kind of experiment, it might be
sufficient to only use a Peltier element 458 or only a heater 566
or a heat exchanging unit. Again, the Peltier element 458 is used
for heating or cooling the temperature inside the temperature
control unit 562. Air is circulated by fan 564 such that a uniform
temperature inside the temperature control unit 562 and the reagent
chamber 150 is achieved. The heater 566 can support the Peltier
element 458 to more rapidly achieving higher temperatures if
necessary.
[0049] The embodiment of FIG. 6 essentially corresponds to the one
of FIG. 5 with the difference that instead of the Falcon tube 380 a
Schott flask 680 is used as a reagent container. Instead of using a
perfusor, a peristaltic pump 676 is used. Peristaltic pumps are
typically used in experiments, like organ-on-a-chip experiments,
where a reagent has to be supplied continuously to a sample while,
at the same time, reagent is removed from the sample. As shown in
FIG. 6, reagent is conveyed through a reagent supply line 254 from
the Schott flask 680 via the peristaltic pump 676 through the
connecting tube 170 and the plug 172 to the sample 120. At the same
time, reagent is removed from the sample 120 via reagent removal
line 656. The removed reagent is transported back into the same or
a second Schott flask 680 or another container.
[0050] It should be noted that this kind of embodiment can also be
implemented in an embodiment shown in FIG. 3 or 4 without having an
external temperature control unit. Any of the embodiments described
in connection with FIGS. 3 to 7 can also be implemented in a
reagent chamber 150 as shown in FIG. 2, namely a reagent chamber
150 integrated into the sample chamber 106.
[0051] FIG. 7 essentially corresponds to FIG. 3 and is only
intended to illustrate the coolpack 360 at the backside of the
reagent chamber 150. Regarding other details, reference is made to
FIG. 3.
[0052] While the invention has been illustrated and described in
detail in the drawings and foregoing description, such illustration
and description are to be considered illustrative or exemplary and
not restrictive. It will be understood that changes and
modifications may be made by those of ordinary skill within the
scope of the following claims. In particular, the present invention
covers further embodiments with any combination of features from
different embodiments described above and below. Additionally,
statements made herein characterizing the invention refer to an
embodiment of the invention and not necessarily all
embodiments.
[0053] The terms used in the claims should be construed to have the
broadest reasonable interpretation consistent with the foregoing
description. For example, the use of the article "a" or "the" in
introducing an element should not be interpreted as being exclusive
of a plurality of elements. Likewise, the recitation of "or" should
be interpreted as being inclusive, such that the recitation of "A
or B" is not exclusive of "A and B," unless it is clear from the
context or the foregoing description that only one of A and B is
intended. Further, the recitation of "at least one of A, B and C"
should be interpreted as one or more of a group of elements
consisting of A, B and C, and should not be interpreted as
requiring at least one of each of the listed elements A, B and C,
regardless of whether A, B and C are related as categories or
otherwise. Moreover, the recitation of "A, B and/or C" or "at least
one of A, B or C" should be interpreted as including any singular
entity from the listed elements, e.g., A, any subset from the
listed elements, e.g., A and B, or the entire list of elements A, B
and C.
LIST OF REFERENCE SIGNS
[0054] 100 Microscope [0055] 102 Microscope housing [0056] 104
Housing section [0057] 106 Sample chamber [0058] 112 Cable duct
[0059] 116 Microscope stage [0060] 118 Illumination optics [0061]
120 Sample [0062] 124 Imaging optics [0063] 150 Reagent chamber
[0064] 152 Door [0065] 170 Connecting tube [0066] 172 Plug [0067]
210 Stage top chamber [0068] 252 Opening [0069] 254 Reagent supply
line [0070] 272 Plug [0071] 360 Coolpack [0072] 380 Reagent
container, Falcon tube [0073] 458 Peltier element [0074] 562
Temperature control unit [0075] 564 Fan [0076] 566 Heating unit,
heater [0077] 656 Reagent removal line [0078] 676 Peristaltic pump
[0079] 680 Reagent container, Schott flask
* * * * *